Biol. Pharm. Bull. 29(2) 216—219 (2006)

Intricate homeostatic mechanisms have been implicated in maintaining the blood glucose concentration over a narrow physiological range. The brain, as well as the peripheral organs such as pancreas, liver, and gastrointestinal tract, is able to sense the nutritional state and secretes specific hormones to maintain metabolic homeostasis. All of these cells contain a high-Km glucose-phosphorylating enzyme, i.e., glucokinase (GK). GK is a member of the hexokinase (HK) family (ATP: Dhexose 6-phosphotransferase, EC 2.7.1.1) that catalyzes the phosphorylation of glucose to glucose 6-phosphate, and is often called HK type IV. HK types I, II, and III have a high affinity (Km 20—130 mM) for glucose and a molecular size of about 100 kDa. In contrast, GK has a low affinity for glucose (Km 5—10 mM), is not inhibited by physiological concentrations of glucose 6-phosphate, and has a molecular size of about 50 kDa. It is widely accepted that GK in pancreatic B-cells plays a critical role in sensing blood glucose and acts as a primary glucose sensor. GK mRNA was detected in the rat brain by real-time reverse transcription polymerase chain reaction (real-time RTPCR) analysis and reported to be localized in various hypothalamic areas, i.e. lateral hypothalamic area (LHA), ventromedial nucleus (VMN), paraventricular nucleus (PVN), dorsomedial nucleus (DMN), and arcuate nucleus (ARN), by use of the in situ hybridization technique. The GK mRNA-expressing areas in the hypothalamus are considered to contain glucose-sensitive or glucose-responsive cells and to play roles in feeding behavior and glucose homeostasis. GK immunoreactivity is also localized in the ependymocytes lining the ventricles and serotonin neurons in the midline medulla. However, no studies have heretofore examined GK activity in each of the hypothalamic nuclei of normal or diabetic animals. In the present study, we measured both the activity and mRNA level of GK in the hypothalamic nuclei and the brain cortex of streptozotocin (STZ)and vehicle-treated rats. MATERIALS AND METHODS